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A bivalent vaccine based on a replication-incompetent influenza virus protects against Streptococcus pneumoniae and influenza virus infection.
- Source :
-
Journal of virology [J Virol] 2014 Nov; Vol. 88 (22), pp. 13410-7. Date of Electronic Publication: 2014 Sep 10. - Publication Year :
- 2014
-
Abstract
- Unlabelled: Streptococcus pneumoniae is a major causative pathogen in community-acquired pneumonia; together with influenza virus, it represents an important public health burden. Although vaccination is the most effective prophylaxis against these infectious agents, no single vaccine simultaneously provides protective immunity against both S. pneumoniae and influenza virus. Previously, we demonstrated that several replication-incompetent influenza viruses efficiently elicit IgG in serum and IgA in the upper and lower respiratory tracts. Here, we generated a replication-incompetent hemagglutinin knockout (HA-KO) influenza virus possessing the sequence for the antigenic region of pneumococcal surface protein A (PspA). Although this virus (HA-KO/PspA virus) could replicate only in an HA-expressing cell line, it infected wild-type cells and expressed both viral proteins and PspA. PspA- and influenza virus-specific antibodies were detected in nasal wash and bronchoalveolar lavage fluids and in sera from mice intranasally inoculated with HA-KO/PspA virus, and mice inoculated with HA-KO/PspA virus were completely protected from lethal challenge with either S. pneumoniae or influenza virus. Further, bacterial colonization of the nasopharynx was prevented in mice immunized with HA-KO/PspA virus. These results indicate that HA-KO/PspA virus is a promising bivalent vaccine candidate that simultaneously confers protective immunity against both S. pneumoniae and influenza virus. We believe that this strategy offers a platform for the development of bivalent vaccines, based on replication-incompetent influenza virus, against pathogens that cause respiratory infectious diseases.<br />Importance: Streptococcus pneumoniae and influenza viruses cause contagious diseases, but no single vaccine can simultaneously provide protective immunity against both pathogens. Here, we used reverse genetics to generate a replication-incompetent influenza virus carrying the sequence for the antigenic region of pneumococcal surface protein A and demonstrated that mice immunized with this virus were completely protected from lethal doses of infection with either influenza virus or Streptococcus pneumoniae. We believe that this strategy, which is based on a replication-incompetent influenza virus possessing the antigenic region of other respiratory pathogens, offers a platform for the development of bivalent vaccines.<br /> (Copyright © 2014, American Society for Microbiology. All Rights Reserved.)
- Subjects :
- Animals
Bacterial Proteins genetics
Bacterial Proteins immunology
Carrier State prevention & control
Disease Models, Animal
Female
Gene Knockout Techniques
Hemagglutinin Glycoproteins, Influenza Virus genetics
Humans
Influenza A virus genetics
Influenza Vaccines administration & dosage
Influenza Vaccines genetics
Nasopharynx microbiology
Orthomyxoviridae Infections immunology
Pneumococcal Infections immunology
Streptococcal Vaccines administration & dosage
Streptococcal Vaccines genetics
Streptococcus pneumoniae genetics
Survival Analysis
Vaccines, Synthetic administration & dosage
Vaccines, Synthetic genetics
Vaccines, Synthetic immunology
Influenza A virus immunology
Influenza Vaccines immunology
Orthomyxoviridae Infections prevention & control
Pneumococcal Infections prevention & control
Streptococcal Vaccines immunology
Streptococcus pneumoniae immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1098-5514
- Volume :
- 88
- Issue :
- 22
- Database :
- MEDLINE
- Journal :
- Journal of virology
- Publication Type :
- Academic Journal
- Accession number :
- 25210171
- Full Text :
- https://doi.org/10.1128/JVI.01205-14